* Professor of Physiology and Medicine, Nabanji Medical Centre, P. O. Box 30243, Lusaka, ZAMBIA.
*Corresponding Author: Nightingale Syabbalo, Professor of Physiology and Medicine, Nabanji Medical Centre, P. O. Box 30243, Lusaka, ZAMBIA.
Citation: Nightingale Syabbalo, (2022). Aerosol Biologics for the Treatment of Eosinophilic Asthma. J Thoracic Disease and Cardiothoracic Surgery, 3(1); DOI:10.31579/2693-2156/035
Asthma is a heterogeneous chronic airway disease comprising of distinct phenotypes characterized by different immunopathophysiologic pathways, clinical features, disease severity, and response to treatment. The phenotypes of asthma include eosinophilic, neutrophilic, mixed cellularity, and paucigranulocytic asthma. Eosinophilic asthma is principally a T helper type 2 (Th2)-mediated airway disease. However, several other immune and structural cells secrete the cytokines implicated in the pathogenesis of eosinophilic asthma. Innate type 2 lymphoid cells, mast cells, basophils, and eosinophils secrete Th2 cytokines, such as interleukin-4 (IL-4), IL-13, and IL-5. Additionally, airway epithelial cells produce alarmin cytokines, including IL-25, IL-33, and thymic stromal lymphopoietin (TSLP). Alarmins are the key initiators of allergic inflammation at the sentinel mucosal surfaces. Innovative biotherapeutic research has led to the discovery of monoclonal antibodies which target and inhibit the immunopathological effects of the cytokines involved in the pathogenesis of eosinophilic asthma. Parenteral biologics targeting the inciting interleukins, include mepolizumab and reslizumab (anti-IL-5), benralizumab (anti-IL-5Rα), dupilumab (anti-4Rα), and tezelizumab (anti-TSLP). They have been shown to significantly reduce annualized exacerbation rates, improve asthma control, lung function, and quality of life. Currently, there are no pulmonary delivered aerosol biologics for topical treatment of asthma. CSJ117 is a potent neutralizing antibody Fab fragment against TSLP, formulated as a PulmoSol TM engineered powder, and is delivered to the lungs by a dry powder inhaler. Phase 2 placebo-controlled clinical trial evaluated the efficacy and safety of CSJ117. CSJ117 delivered as an inhaler attenuated the late asthmatic response (LAR), and the early asthmatic response (EAR) after allergen inhalation challenge (AIC) at day 84 of treatment. The maximum decrease in FVE1 from pre-AIC were significantly lower in the CSJ117 group compared to placebo (P = 029), during LAR. CSJ117 also significantly reduced fractional exhaled nitric oxide before AIC at day 83; and significantly reduced the allergen-induced increase in % sputum eosinophil count. Pulmonary delivery of biologics directly to the airway mucosal surface has several advantages over parenteral routes, particularly in treating airway diseases such as asthma. Inhaler delivered biologics, such as CSJ117 are innovative and attractive methods of future precision treatment of asthma, and other respiratory diseases.
Introduction
Asthma is a significant public health, and socio-economical problem affecting more than 358 million individuals worldwide [1]. It is a heterogeneous chronic airway disease encompassing distinct phenotypes characterized by different immunopathophysiological pathways, clinical features, disease severity, physiology, and response to treatment. The phenotypes of asthma include eosinophilic, neutrophilic, mixed cellularity, and paucigranulocytic asthma. Eosinophilic asthma is principally a T helper type 2 (Th2)-mediated disease. However, several other immune, such as innate type 2 lymphoid cells (ILC2s), mast cells, basophils, and eosinophils; and structural cells, including fibroblasts, myofibroblasts, and airway smooth muscle cells also secrete the cytokines, and chemokines implicated in the pathogenesis of eosinophilic asthma. Dysfunctional and injured airway epithelial cells exude a special type of cytokines termed alarmins, including IL-25, IL-33, and thymic stromal lymphopoietin (TSLP). Alarmins are the key initiators of allergic eosinophilic inflammation at the sentinel mucosal surfaces. Because there are several types of immune, and structural cells secreting cytokines promoting eosinophilic inflammation, eosinophilic asthma is also termed as Th2-high asthma, in contrast to Th2-low neutrophilic, and paucigranulocytic asthma.
Despite national guidelines [1-3], and innovative therapies, such as single dual inhaler or single triple inhaler therapy [4-7], about 3.6-10% of the patients with asthma are unresponsive to the standard of care therapy [8-10]. Precise understanding of the pathophysiological mechanisms, and pathways involved in the pathogenesis of asthma has led to the innovate discovery of biologics for add-on treatment of severe, uncontrolled eosinophilic asthma.
A repertoire of biologics are currently available for the treatment of severe, uncontrolled eosinophilic asthma [11-15].
Parenteral administered biologics targeting the inciting interleukins in the pathogenesis of asthma, include omalizumab (anti-IgE), mepolizumab and reslizumab (anti-IL-5), benralizumab (anti-IL-5Rα), dupilumab (anti-4Rα), and tezelizumab (anti-TSLP). However, monoclonal antibodies (mAb) are less effective in the treatment of other phenotypes of asthma with low blood eosinophil counts, and low fractional exhaled nitric oxide (FeNO) levels, such as neutrophilic, and paucigranulocytic asthma [16-19]. Moreover, omalizumab [20], mepolizumab and benralizumab [21], and dupilumab [22, 23] therapies reduce exacerbations by about 50%, and are unable to eliminate exacerbations completely. Discontinuation of the biologics may result in poor asthma control, and even worse symptoms, and frequent exacerbations. Thus, there is still unmet need to explore for novel biologics capable of treating most of the phenotypes of asthma, and to prevent airway remodeling, and fixed severe airflow limitation. (Table 1) depicts the dosages of the approved biologics for the treatment of severe eosinophilic asthma.
Biologic
Dosage
Efficacy
Omalizumab*
75-375 mg SC Q 2/4 wk
Reduces exacerbations (47-53%)
Mepolizumab*
100 mg SC Q 4 wk
Reduces exacerbations (50-60%)
Reslizumab
3 mg/kg IV Q 4 wk
Reduces exacerbations (34-75%)
Benralizumab*
30 mg SC Q 8 wk
Reduces exacerbations (25-60%)
Dupilumab*
300 mg SC Q 2 wk
Reduces exacerbations (60-80%)
Tezepelumab*
210 mg SC Q 4 wk
Reduces exacerbations (41-56%)
Abbreviations: IV, intravenous, given over 25-50 min; SC, subcutaneous, Q, every; wk, weeks. * Approved for childhood asthma. Pediatric dosages depend on age and body weight of the child or adolescent.
Table 1: Dosages of approved biologics by the Food and Drug Administration for the treatment of severe asthma
Results
Airway epithelial cells play a key role in the regulation of tissue homeostasis by producing and secreting several proteins, such as antioxidants, lipid mediators, cytokines, chemokines, and growth factors [24, 25]. Damaged, and dysfunctional epithelium produce large quantities of cytokines, and growth factors that interact with the underlying mesenchymal cells, including fibroblasts, and myofiblobasts to induce epithelial-mesenchymal transition (EMT), promote airway remodeling [26-28], resulting in persistent airway obstruction [26].
The epithelial-derived cytokines (also termed alarmins), such as interleukin-25 (IL-25) [29-31], IL-33 [31-34], and thymic stromal lymphopoietin (TSLP) [31,35-38] play an initiating key role in the pathogenesis of eosinophilic asthma. Alarmin cytokine secretion can be aroused by respiratory viral, bacterial, and fungal infections, allergens, proteases, chemical irritants, mechanical injury, and cytokines, such as TNF-α, IL-1β [24,29]. Epithelial-derived cytokines secretion during viral respiratory infections is the major trigger of asthma exacerbations, particularly in children [39,40].
Biologics targeting alarmin cytokines have a potential to prevent, and efficaciously treat asthma, and exacerbations [41-45]. Inhibiting upstream alarmin cytokines by specific monoclonal antibodies is a very effective strategy capable of interfering with the downstream inflammatory cascades resulting in eosinophilic asthma [41,46]. Current biologics are not disease modifying, and discontinuing treatment with these biologics result in return of the severity of asthma to pre-treatment levels, or even worsening of asthma control [47,48]. Blocking alarmins, has the potential to inhibit EMT, airway hyperresponsiveness, and remodeling, thus preventing decline in lung function, and persistent severe eosinophilic asthma [42].
Currently, there are no biologics targeting IL-25, and IL-33 approved for the treatment of eosinophilic asthma. Itepekimab is a human IgG4P monoclonal antibody targeting IL-33. Wechsler et al. [49] have shown that a single subcutaneous injection of itepekimab 300 mg reduces exacerbations, and improve asthma control, lung function (FEV1), and health-related quality of life (HLQoL). The efficacy of itepekimab was almost similar to that achieved by dupilumab, although the outcomes were slightly less. However, dual itepekimab plus dupilumab treatment did not result in any clinical and statistical improvement in asthma control, and lung function.
Tezepelumab is a first-in class fully-human IgG2ʎ monoclonal antibody that binds to TSLP, thus blocking its interaction with the TSLP heterodimeric receptor, TSLPR, henceforth inhibiting multiple downstream inflammatory pathways [50,51]. Tezepelumab administered as add-on therapy has been shown to be efficacious, safe, and well tolerated by patients with severe uncontrolled asthma, regardless of the phenotype of asthma. Several clinical trials have documented that tezepelumab significantly reduces exacerbations by about 71%, and improve asthma control, lung function [52,53], and HLQoL in patients with severe, uncontrolled asthma [52]. Subgroup analysis of the PATHWAY study revealed that the reductions in annualized asthma exacerbation rates (AAER) were significant irrespective of patient phenotype, as assessed by blood eosinophil count (˂ 150 cells/µL), ≥ 150 cells/µL, < 300>
Pham et al. [54] re-analysis of the PATHWAY data showed that tezepelumab reduced blood eosinophil count, serum IgE, and FeNO levels; and Th2 cytokines, including IL-5, and IL-13 in patients with severe, uncontrolled asthma. Based on the findings from the PATHWAY studies, tezepelumab was granted Breakthrough Therapy Designation by the US Food and Drug Administration (FDA) in 2019 for patients with severe asthma without an eosinophilic phenotype, who were receiving ICS/LABA with or without OCS, and additional asthma controllers [55].
Phase III NAVIGATOR multi-centre, randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of tezepelumab in 1061 patients aged 12 to 80 years with severe, uncontrolled asthma [56]. Tezepelumab significantly reduced the annualized asthma exacerbation rate by more than half in this broad group of patients (P ˂ 0.001). The AAER average was 0.9 in the 529 patients who received tezepelumab versus 2.10 for the 532 patients who received placebo in the 52 week trial. Tezepelumab also significantly improved lung function. Pre-bronchodilator FEV1 improved from baseline by about 0.23 L on average with tezepelumab, and by a mean of 0.09 L in patients who received placebo (P ˂ 0.001). Furthermore, tezepelumab treatment reduced the rate of emergency department visits by fivefold, and hospitalization by 85%. Notably, there was significant improvement in the Asthma Control Questionnaire-6 (ACQ-6), and the Asthma Quality of Life Questionnaire (AQLQ) scores [56]. This shows that tezepelumab is efficacious and safe for the treatment of adolescents and adults with severe, uncontrolled asthma.
Post-hoc analysis of phase 2b PATHWAY multicentre, randomized, double-blind, placebo-controlled study of 555 patients aged 18-75 years with severe, uncontrolled asthma with or without nasal polyps (NP) revealed that tezepelumab reduced AAER in both groups of patients [57]. Patients who received placebo with asthma and NP, and asthma without NP had higher AAER compared to those treated with tezepelumab [56]. The AAER was reduced to a similar extent in both groups of patients with asthma and NP, and asthma without NP who received tezepelumab 210 mg. The reduction in AAER for patients with asthma and NP was 75%, and the reduction in AAER was 73% in patients with asthma without NP. In both groups of patients who received placebo, patients experienced one to three more exacerbations than in the tezepelumab 210 mg group. Furthermore, treatment with tezepelumab 210 mg resulted in decrease in blood eosinophil counts, and FeNO levels compared to placebo [57].
Exploratory analysis of the NAVIGATOR phase III trial has demonstrated that tezepelumab reduced exacerbations, and improved lung function; and nasal symptoms in patients with severe, uncontrolled asthma with nasal polyps [58]. Tezepelumab reduced AAER by 86% in patients with asthma and nasal polyposis, and by 52% in patients with asthma without nasal polyposis over 52 weeks, compared to placebo. Tezepelumab improved lung function at week 52 in both groups of patients with an increase in pre-bronchodilator FEV1 of 0.20 L in the patients with asthma and NP, and 0.13 L in patients with asthma without NP. Concomitantly, tezepelumab significantly improved symptoms of nasal polyps at week 52. It significantly reduced the SinoNasal Outcome Test (SNOT-22, [59]) scores in patients with asthma and nasal polyps by 9.6 points versus placebo. The adjusted mean scores reduction from baseline for tezepelumab was 20.10 points, and for placebo was 10.55 points. The baseline mean (± sd) SNOT-22 scores for tezepelumab was 49.4 ± 21.5, and for placebo was 47.8 ± 19.0 [56]. Thus, demonstrating that tezepelumab may also be effective in the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) [58]. Tezepelumab is in phase 3 clinical trials for the treatment of CRSwNP.
The results from the NAVIGATOR trial exploratory analysis are exciting [58]. Patients with eosinophilic asthma and comorbid chronic rhinosinusitis with nasal polyps have more severe united airway disease than patients with eosinophilic asthma or CRSwNP alone [57,60]. Asthmatic patients with CRSwNP experience frequent exacerbations, hospitalization, emergency department visits; and have poor lung function, and HLQoL [61,62]. On the other hand, patients with CRSwNP and asthma have persistent severe nasal obstruction, hyposmia, sleep disturbance, anxiety, and depression, and worse HLQoL [63-65]. They are often corticosteroid dependent, and require frequent functional endoscopic nasal surgery for nasal polyps [66,67].
Treatment of severe eosinophilic asthma with comorbid CRSwNP is challenging. Such patients require a universal targeted therapy, such as biologics, and in particular biologics delivered directly to the nasal airways, and tracheobronchial tree. Currently, there are no approved intranasal or inhaler biologics for the treatment of eosinophilic asthma, and CRSwNP. Noteworthy, dupilumab [68], and omalizumab [69] which are administered subcutaneously are approved for the treatment of both eosinophilic asthma, and CRSwNP.
Discussion
Pulmonary Delivery of Aerosol Biologics
Biological drugs (synonymous known as biologics) are a diverse group of therapeutic agents which are large and complex molecules produced through sophisticated biotechnology [70, 72]. The biologics currently used to treat severe asthma are monoclonal antibodies, and antibody fragments, which are administered subcutaneously, or intravenously (reslizumab). Injection of drugs is painful and inconvenient, especially when the drugs are for the treatment of chronic diseases, such as asthma, and alpha-1 antitrypsin deficiency [73, 74]. Moreover, 10% of the patients worldwide suffer from needle phobia leading to poor compliance [75]. Pulmonary delivery of biologics to the lungs improve pharmacokinetics, and toxicity profiles of proteins. It is a non-invasive route, and allows for self-administration, which could improve patient compliance [76].
Pulmonary delivery of biologics is an attractive non-invasive route of administration for the treatment of respiratory diseases [76-79], such as asthma [80-84], cystic fibrosis [85, 86], alpha-1 antitrypsin deficiency (AATP) [87,88], pulmonary alveolar proteinosis (PAP) [89,90], lung cancer [91,92], and SARS-CoV-2 [93-95]. Pulmonary delivery of biologics is also an alternative route for administering biologics for the treatment of non-respiratory systemic diseases, including diabetes mellitus [96-98], anaemia [99], and multiple sclerosis [100]. The development of inhalation biologics, and design of methods of inhalation technology are outside the scope of this manuscript, but excellent information can be found in references [76-79]. Table 2 shows preclinical trials of aerosol biologics for the treatment of respiratory diseases, and non-respiratory systemic diseases.
Table 2: Preclinical trials of aerosol biologics in respiratory diseases, and non-respiratory systemic diseases
The large surface area, and the extensive vascularization of the airways, and lungs enable rapid absorption, and fast onset of action of drugs delivered to the lungs [101]. Pulmonary delivery also offers the advantage of delivering biologics at high concentration in the lungs, and directly to inflammatory cells, and has the potential to achieve high blood levels of the biologics. Additionally, there is a lower level of proteolytic enzymatic activity in the lung, and minimal first-pass metabolism [76], hence higher concentrations of the biologics in the airways, and lung parenchyma.
However, despite the beneficial effects of pulmonary delivery of biologics, it requires innovative biotechnology to develop biologics, and inhaler devices to propel the biologics to the tracheobronchial tree, and lung parenchyma [76-79]. Furthermore, there are anatomical, physiological, and immunological factors that affect the pharmacodynamics, and biotherapeutic efficacy, and safety of inhaled biologics [102]. The other obstacle is the formulation of biologics for delivery into the lungs [78,79, 103]. Three methods have been applied to modify the structure, aerodynamic diameter (Dae), shape, hydroscopicity, and density of biologics to enhance their absorption through the mucociliary blanket, pharmacokinetics, and bioavailability [104,105]. They include antibody fragment development [106,107], Fc engineering [108,109], and pegylation [110,111]. Pegylation protects proteins from renal clearance and proteolytic degradation, thus prolongs protein local residence time, and bioavailability in the body [110]. Pegylation has been shown to be an effective method for extending the retention time of biologics in the lung, such as human alpha-1 proteinase inhibitor (α1-PI) [112], IFN-α [113], and antibody fragments [114,115].
The type of inhaler has critical importance for the delivery of biologics, because 75% of inhaled protein formulations in clinical research are produced as liquids [76]. There are four main types of inhalers for the delivery of orally inhaled proteins, peptides, and cytokines, such as pressure metered dose inhalers (PMDI), dry powder inhalers (DPI), soft mist inhalers (SMI), and nebulizers [77,79,116-120].
Most biologics in clinical trial for the treatment of asthma have been delivered to the lung by DPIs. However, SMIs are novel multidose propellant-free, handheld inhalers, and are more suitable for delivery of biologics than pMDI [79]. The most experience of pulmonary delivery of biologics with DPIs has been the Exubera® and Technosphere® insulin (Afrezza®), for the treatment of diabetes mellitus [121]. Currently, three DPIs have been utilized in clinical trials for the delivery of biologics to the lungs. They include the F1P for administration of the anti-IL-13 monoclonal antibody fragment VR942 (Abrezekimab) [102]; Cyclohaler® (single dose, PB Pharma GmbH, Meerbusch, German) for the administration of DAS181 (Fludase®) [122]; and Concept1 (single dose, Norvatis, Basel, Switzerland) (NCT4410523) for administration of the anti-thymic stromal lymphopoietin monoclonal antibody Fab fragment CSJ117 [84,123]. Biotechnological modification of proteins and peptides, and proper inhaler devices can be successfully used to deliver biologics which are effective, and immunologically safe for the treatment of airway diseases, pulmonary diseases, and systemic diseases.
The precise mechanism by which mAb, and antibody fragments exert their immunotherapeutic effects is by inhibiting surface receptors on immune and inflammatory, and immune cells, thus preventing these cells from secreting cytokines, chemokines, and adhesion molecules. Several mAb, and antibody fragments are currently in preclinical and clinical trials for the treatment of eosinophilic asthma [81-83,120,122-126], and neutrophilic asthma [127]. However, CSJ117 has demonstrated very encouraging and promising results.
Csj117 Dpi for the Treatment of Eosinophilic Asthma CSJ117 is a potent neutralizing antibody Fab fragment against TSLP. It is formulated as a PulmoSol TM engineered powder in hard capsules for delivery to the lungs by a dry powder inhale (DPI). Phase 2 double-blind, placebo-controlled clinical trial evaluated the efficacy and safety of CSJ117 on the late asthmatic response (LAR), the early asthmatic response (EAR), and biomarkers of eosinophilic asthma after allergen inhalation challenge (AIC) [84,128]. CSJ117 significantly attenuated the LAR and EAR at day 84 of treatment. The maximum decrease in FVE1 from pre-AIC were significantly lower in the CSJ117 group compared to placebo (P = 029), during LAR. CSJ117 also significantly reduced fractional exhaled nitric oxide before AIC at day 83; and significantly reduced the allergen-induced increase in % sputum eosinophil count [84]. This study demonstrates the potential of inhaled biologics, particularly those targeting the alarmin cytokines in the treatment and prevention of eosinophilic asthma. Aerosol CSJ117 by acting topically and blocking the immunopathological effects of TSLP may become the precise asthmatic drug delivery in the nearby future.
Conclusion
Eosinophilic asthma is principally a Th2-mediated airway disease. Th2 lymphocytes, ILCs, mast cells, and eosinophils secrete inflammatory cytokines, such as IL-4, IL-13, and IL-5 which promote airway inflammation, AHR, and remodeling. Additionally, dysfunctional epithelial cells exude alarmin cytokines, including IL-25, IL-33, and TSLP which further amplifies the inflammatory cascade, and airway remodeling. Patients with eosinophilic asthma respond favorably to targeted mAb, such as omalizumab, mepolizumab, dupilumab, and tezepelumab. However, biologics do not modify progressive airway remodeling which is responsible for severe asthma. Conventionally, asthma is best treated with locally-acting aerosol inhalers, such as LABA, ICS, and single triple inhaler therapy. Currently, there are no aerosol biologics for the treatment of asthma. CSJ117 is a potent neutralizing antibody Fab fragment against TSLP, formulated as a PulmoSol TM engineered powder, and is delivered to the lungs by a dry powder inhaler. CSJ117 delivered as an inhaler has been shown to attenuate the late asthmatic response, and the early asthmatic response after allergen inhalation challenge at day 84 of the treatment. CSJ11 significantly improved pre-AIC lung function (FEV1) compared to placebo. Additionally, CSJ117 significantly decreased inflammatory biomarkers of eosinophilic asthma, such as allergen-induced increase in % sputum eosinophil count, and FeNO. Pulmonary delivery of aerosol biologics to the lungs is a precise targeted route of drug administration to treat patients with eosinophilic asthma.
Conflicts of Interest
The author declares that the publication was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Abbreviations
AAER : Annualized asthma exacerbation rates AATP : Alpha-1 anti-trypsin deficiency ACQ-6 : Asthma Control Questionnaire-6 AHR :Airway hyperresponsiveness AIC : Allergen inhalation challenge ALI : Acute lung injury AQLQ : Asthma Quality of Life Questionnaire ARDS : Acute respiratory distress syndrome BOOP : Bronchiolitis obliterans organizing pneumonia COPD : Chronic obstructive pulmonary disease COVID-19: Coronavirus Disease 19 CRSwNP: Chronic rhinosinusitis with nasal polyps Dae : Aerodynamic diameter DPI : Dry powder inhaler AER : Early asthmatic response EMT : Epithelial-mesenchymal transition FeNO : Fractional exhaled nitric oxide FEV1 : forced expired volume in one second HLQoL : Health-related quality of life ICS : Inhaled Corticosteroid IgE : Immunoglobulin E IL : Interleukin ILCs : Innate type 2 lymphoid cells LABA : Long-acting beta-2 agonist LAR : Late asthmatic response mAb : monoclonal antibody OCS : Oral Corticosteroid PAP : Pulmonary alveolar proteinosis PMDI : Pressure metered dose inhaler RSV : Respiratory syncytial virus SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2 SNOT-22: SinoNasal Outcome Test 22 Th2 : T helper type 2 lymphocytes TNF-α : Tumor necrosis factor-α TSLP : thymic stromal lymphopoietin
References
Global Initiative for Asthma. (2020) Global Strategy for Asthma Management and Prevention. - updated 2020. www.ginaasthma.org. View at Publisher |
View at Google Scholar
Cloutier MM, Baptist AP, Blake KV, et al. (2020) Expert Panel Working Group of the National Heart, Lung, and Blood Institute. 2020 Focused updates to the asthma management guidelines: a report from the National Asthma Educational and Preventive Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol 146(6):1217-1270. doi: 10.1016/j.jaci.2020.10.003. View at Publisher |
View at Google Scholar
Cloutier MM, Dixon AE, Krishnan JA, Lemanske RF Jr, Pace W, Schatz M. (2020) Managing asthma in adolescents and adults: 2020 asthma guideline update from the National Asthma Education and Prevention Program. JAMA 324(22):2301-2317. doi: 10.1001/jama.2020.21974. View at Publisher |
View at Google Scholar
Virchow JC, Kuna P, Paggiaro P, Papi A, Singh D, Corre S, et al. Single inhaler extrafine triple therapy in uncontrolled asthma (TRIMARAN and TRIGGER): two double-blind, parallel-group, randomised, controlled phase 3 trials. Lancet 394(10 210):1737-1749. doi: 10.1016/S0140-6736(19)32215-9. View at Publisher |
View at Google Scholar
Singh D, Cruz AA, Canonica GW, Vele A, Kots M, Georges G, Papi A. Extrafine triple therapy in patients with asthma and persistent airflow limitation. Eur Respir J 2020; 56:2000476; DOI: 10.1183/13993003-00476-2020. View at Publisher |
View at Google Scholar
Lee LA, Bailes Z, Barnes N, Boulet L-P, Edwards D, Fowler A, Hanania N, Kerstjens HB, et al. (2020) Efficacy and safety once-daily single-inhaler triple therapy (FF/UMEC/VI versus FF/VI in patients with inadequately controlled asthma (CAPTAIN): a double-blind, randomised, phase 3A trial. Lancet Respir Med DOI: https://doi.org/10.1016/S2213-2600(20)30389-1. View at Publisher |
View at Google Scholar
Kim LHY, Saleh C, Whalen-Browne A, et al. (2021) Triple vs dual inhaler therapy and asthma outcomes in moderate to severe asthma: a systematic review and meta-analysis. JAMA doi: 10.1001/jama.2021.7872. View at Publisher |
View at Google Scholar
Holgate ST, Polosa R. (2006) The mechanisms, diagnosis, and management of severe asthma in adults. Lancet 368:780-793. View at Publisher |
View at Google Scholar
Moore WC, Bleecker ER, Curran-Everett D, Erzurum SC, Ameredes BT, Bacharier L, et al. (2007) National Heart, Lung, Blood Institute’s Severe Asthma Program. Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute’s Severe Asthma Research Program. J Allergy Clin Immunol 119:405-413. View at Publisher |
View at Google Scholar
Peters MC, Kerr S, Duncan EM, Woodruff PG, Fajt ML, Levy BD, Israel E, Phillips BR, et al; National Lung and Blood Institute Severe Asthma Research Program-3. Refractory airway type-2 inflammation in a large subgroup of asthmatics treated with inhaled corticosteroids. J Allergy Clin Immunol 2018; pii: S0091-6749(18)30390-7. doi: 10.1016/jaci.2017.12.1009. View at Publisher |
View at Google Scholar
McCracken J, Tripple J, Calhourn WJ. (2016) Biologic therapy in the management of asthma. Curr Opin Allergy Clin Immunol 16(4):375-382. doi: 10.1097/ACI.0000000000000284. View at Publisher |
View at Google Scholar
Pepper AN, Renz H, Casale TB, Garn H. (2017) Biologic therapy and novel molecular targets of severe asthma. J Allergy Clin Immunol 5:909-915. DOI: https://doi.org/10.1016/j.jaip.2017.04.038. View at Publisher |
View at Google Scholar
McGregor MC, Krings JG, Nair P, Castro M. Role of biologics in asthma. (2019) Am J Respir Crit Care Med 199(4):433-445. doi: 10.1164/rccm.201810-1944Cl. View at Publisher |
View at Google Scholar
Syabbalo N. (2021) Biologics for the treatment of severe childhood asthma. J Thorac Dis Cardiothorac Surg 2(2); 31579/2693-2156/024. View at Publisher |
View at Google Scholar
Hanania NA, Wenzel S, Rosen K, Hsieh HJ, Mosesova S, Choy DF, Lal P, Arron JR, Harris JM, Busse W. (2013) Exploring the effects of omalizumab in allergic asthma: an analysis of biomarkers in the EXTRA study. Am J Respir Crit Care Med 187:804-811. View at Publisher |
View at Google Scholar
Busse WW, Bleecker ER, FitzGerald JM,Bora study investigators. (2019) Long-term safety and efficacy of benralizumab in patients with severe, uncontrolled asthma: 1-year results from the BORA phase 3 extension trial. Lancet Respir Med 7:46-59. View at Publisher |
View at Google Scholar
Castro M, Corren J, Pavord ID, Maspero J, Wenzel S, Rabe KF, Busse WW, Ford L, Sher L, FitzGerald JM, et al. (2018) Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N Engl J Med 378:486-496. View at Publisher |
View at Google Scholar
Normansell R, Walker S, Milan SJ, Walters EH, Nair P. (2014) Omalizumab for asthma in adults and children. Cochrane Database Syst Rev (1):CD003559. View at Publisher |
View at Google Scholar
Farne HA, Wilson A, Powell C, Bax L, Milan SJ. (2017) Anti-IL5 therapies for asthma. Cochrane Database Syst Rev 9:CD010834. View at Publisher |
View at Google Scholar
Zayed Y, Kheiri B, Banifadel M, Hicks M, Aburahma A, Hamid K, Bachuwa G, Chandran A. (2018) Dupilumab safety and efficacy in uncontrolled asthma: a systematic review and meta-analysis of randomized clinical trials. J Asthma 56:1-10. View at Publisher |
View at Google Scholar
Xiong XF, Zhu M, Wu HX, Fan LL, Cheng DY. (2019) Efficacy and safety of dupilumab for the treatment of uncontrolled asthma: a meta-analysis of randomized clinical trials. Respir Res 20:108. View at Publisher |
View at Google Scholar
Bartemes KR, Kita H. (2012) Dynamic role of epithelium-derived cytokines in asthma. Clin Immunol 143(3):222-235. doi: 10.1016/j.clim.2012.03.001. View at Publisher |
View at Google Scholar
Syabbalo N. (2020) Airway epithelial dysfunction contributes to the pathogenesis of asthma. J Lung Pulmonol Respir Res 7(4):101-105. View at Publisher |
View at Google Scholar
Holgate ST, Holloway J, Wilson S, Bucchieri F, Puddicombe S, Davis DE. (2004) Epithelial mesenchymal communication in pathogenesis of chronic asthma. Proc Am Thorac Soc 1(2):93-98. View at Publisher |
View at Google Scholar
Hackett T-L, Warner SM, Sefanowicz D, Shaheen F, Pechkovsky DV, Murray LA, Argentieri R, et al. (2009) Induction of epithelial-mesenchymal transition in primary airway epithelial cells from patients with asthma by transforming growth factor-β1. Am J Respir Crit Care Med 180(2):122-133. doi.org/10.1164/rccm.200811-1730OC. View at Publisher |
View at Google Scholar
Hacket T-L. Epithelial-mesenchymal transition in the pathophysiology of airway remodeling in asthma. Curr Opin Immunol 2012; 12(1):53-59. doi: 10.1097/ACI.0b013e3283ec6e6. View at Publisher |
View at Google Scholar
Mitchell PD, O’Byrne PM, Epithelial derived cytokines in asthma. Chest 2017; 151(6):1338-1344. doi: 10.1016/j.chest.2016.10.042. View at Publisher |
View at Google Scholar
Roan F, Obata-Ninomiya K, Ziegler SF. (2019) Epithelial-derived cytokines: More than just signaling the alarm. J Clin Investig 129:1441-1451. View at Publisher |
View at Google Scholar
Hong H, Liao S, Chen F, Yang Q, Wang DY. Role of IL-25, IL-33, and TSLP in triggering united airway diseases toward type 2 inflammation. Allergy 2020; 75:2794-2804. View at Publisher |
View at Google Scholar
Cherry WB, Yoon J, Bartemes KR, Iijima K, Kita A. (2008) A novel IL-1 family cytokine, IL-33, potentially activates human eosinophils. J Allergy Clin Immunol 121:1484-1490. doi: 10.1016/j.jaci.2008.04.005. View at Publisher |
View at Google Scholar
Louten J, Rankin AL, Li Y, Murphy EE, Beaumont M, Moon C, et al. (2011) Endogenous IL-33 enhances Th2 cytokine production and T-cell responses during allergic airway inflammation. Int Immunol 23:307-315. View at Publisher |
View at Google Scholar
Cayrol C, Girard JP. IL-33: (2012) an alarmin cytokine with crucial roles in innate immunity, inflammation and allergy 2014; 31:31-37. https://doi.org/1016/j.coi.2014.09.004. View at Publisher |
View at Google Scholar
Zhang Y, Zhou B. (2012) Functions of thymic stromal lymphopoietin in immunity and disease. Immunol Res 52(3):211-223. View at Publisher |
View at Google Scholar
Watson B, Gauvreau GM. (2014) Thymic stromal lymphopoietin: a central regulator of allergic asthma. Expert Opin Ther Targets 18(7):771-785. View at Publisher |
View at Google Scholar
Ziegler SF, Roan F, Bell BD, Stoklasek TA, Kitajima M, Han H. (2013) The biology of thymic stromal lymphopoietin (TSLP). Adv Pharmacol 66:129-155. doi: 10.1016/B978-0-12-404717-4.00044-4. View at Publisher |
View at Google Scholar
Adhikary PP, Tan Z, Page BDG, Hedtrich S. (2021) TSLP as a druggable target-A silver-lining for atopic diseases? Pharmacol ther 217:107648. View at Publisher |
View at Google Scholar
Johnston SL, Pattemore PK, Sanderson G, et al. (1995) Community study of role of viral infections in exacerbations of asthma in 9-11 year old children. BMJ 310:1225-1229. View at Publisher |
View at Google Scholar
Busse WW, Lemanske RF Jr, Gern JE. (2010) Role of viral respiratory infections in asthma and asthma exacerbations. Lancet 376(9743):826-834. DOI: https://doi.org/10.1016/S0140-6736(10)61380-3. View at Publisher |
View at Google Scholar
Pelaia C, Pelaia G, Longhini F, Crimi C, Calabrese C, Gallelli L, Sciacqua A, Vatrella A. (2021) Monoclonal antibodies targeting alarmins: a new perspective for biological therapies of severe asthma. Biomedicines 9(9): https://10.3390/biomedicines909118. View at Publisher |
View at Google Scholar
Gauvreau GM, White L, Davis BE. (2020) Anti-alarmins entering clinical trials. Curr Opin Pulm Med 26:69-76. doi. 10.1097/MCP0000000000000615. View at Publisher |
View at Google Scholar
Porsbjerg CM, Sverrild A, Lloyd CM, Menzies-Gow AN, Bel EH. (2020) Anti-alarmins in asthma: Targeting the airway epithelium with next generation biologics. Eur Respir J 56:2000260; DOI: 10.1183/13993003.00260-2020. View at Publisher |
View at Google Scholar
Pelaia C, Crimi C, Vatrella A, Tinello C, Terracciano R, Pelaia G. (2020) Molecular targets for biological therapies of severe asthma. Front Immunol 11:603312. View at Publisher |
View at Google Scholar
Albrecht M. (2021) Targeting alarmins and other epithelial mediators of allergic inflammation with biologics. Allergol Select 5:82-88. View at Publisher |
View at Google Scholar
Ortega H, Lemiere C, Llanos JP, et al. (2019) Outcomes following mepolizumab treatment discontinuation: real-world experience from an open-label trial. Allergy Asthma Clin Immunol 15:37. doi: 10.1186/s13223-019-0348.z. View at Publisher |
View at Google Scholar
Haldar P, Brightling CE, Singapuri A, et al. (2014) Outcomes after cessation of mepolizumab therapy in severe eosinophilic asthma: a 12-month follow-up analysis. J Allergy Clin Immunol 133:921-923. doi: 10.1016/j.jaci.2013.11.026. View at Publisher |
View at Google Scholar
Wechsler ME, Ruddy MK, Pavord ID, Isreal E, Rabe KF, Ford LB, Maspero JF, Abdulai RM, Hu C-C, et al. (2021) Efficacy and safety of itekepemab in patients with moderate-to-severe asthma. N Engl J Med 385:1656-1668. DOI: 10.1056/NEJMoa2024257. View at Publisher |
View at Google Scholar
Verstraete K, Peelman F, Braun H, Lopez J, Van Rompaey D, Dansercoer A, Vandenberghe I, Pauwels K, Tavernier J, Lambrecht BN, et al. (2017) Structure and antagonism of the receptor complex mediated by human TSLP in allergy and asthma. Nat Commun 8:14937. doi: 10.1038/ncomms14937. View at Publisher |
View at Google Scholar
Matera MG, Rogliani P, Calzetta L, Cazzola M. (2020) TSLP inhibitors for asthma: current status and future prospects. Drugs 80:449-459. View at Publisher |
View at Google Scholar
Corren J, Parnes JR, Wang L, Mo M, Roseti SL, Griffiths JM, et al. (2017) Tezepelumab in adults with uncontrolled asthma. N Engl J Med 377:936-946. doi: 10.1056/NEJMoa1704064. View at Publisher |
View at Google Scholar
Corren J, Garcia GE, Parnes JR, Pham TH, Griffiths JM. (2019) Tezepelumab treatment effect on annualized rate of exacerbations by baseline biomarkers in uncontrolled severe asthma patients: phase 2b PATHWAY study. Am J Respir Crit Care Med 199:A2621. View at Publisher |
View at Google Scholar
Pham T-H, Ren P, Parnes JR, Griffiths JM. (2019) Tezepelumab reduces multiple key inflammatory biomarkers in patients with severe, uncontrolled asthma in the phase 2b PATHWAY study. Am J Respir Crit Care Med 199:A2677. View at Publisher |
View at Google Scholar
AstraZeneca, Tezepelumab granted Breakthrough Therapy Designation by US FDA.[https://www.astrazeneca.com/media-centre/press-releases/2018/tezepelumab-granted-breakthrough-therapy-designation-by-us-fda-07092018.html]. View at Publisher |
View at Google Scholar
Menzies-Gow, Corren J, Bourdin A, Chupp G, Israel E, Wechsler ME, Brightling CE, Griffiths JM, et al. (2021) Tezepelumab in adults and adolescents with severe, uncontrolled asthma. N Engl J Med DOI: 10.1056/NEJMoa2034975. View at Publisher |
View at Google Scholar
Emson C, Corren J, Salapa K, Hellquist A, Parnes JR, Colice G. (2021) Efficacy of tezepelumab in patients with severe, uncontrolled asthma with or without polyps: a post-hoc analysis of the phase 2b PATHWAT study. J Asthma 14:91-99. doi: 10.2147/JAA.S288260. View at Publisher |
View at Google Scholar
Menzies-Gow A, et al. (2021) Tezepelumab efficacy in patients with severe, uncontrolled asthma and comorbid nasal polyps in NAVIGATOR. ERS poster number: PA876. Poster presentation at the European Respiratory Society (ERS) International Congress 5 September 13:15-14:15 CEST. View at Publisher |
View at Google Scholar
Hopkins C. (2009) Psychometric validity of the 22-item Sinonasal Outcome Test. Clinical Otolaryngology 34:447-454. View at Publisher |
View at Google Scholar
Bilodeau L, Boulay ME, Prince P, Boisvert P, Boulet LP. (2010) Comparative clinical and airway inflammatory features of asthmatics with or without polyps. Rhinology 48(4):420-425. doi: 10.4193/Rhino09.095. View at Publisher |
View at Google Scholar
ten Brinke, Grootendorst DC, Schmidt JT, et al. (2002) Chronic sinusitis in severe asthma is related to sputum eosinophilia. J Allergy Clin Immunol 109: 621-626. View at Publisher |
View at Google Scholar
Halawi AM, Smith SS, Chandra RK. Chronic rhinosinusitis: epidemiology and cost. Allergy asthma Proc 2013; 34:328-334. View at Publisher |
View at Google Scholar
Mendelsohn D, Jeremic G, Wright ED, Rotenberg BW. (2011) Revision rates after endoscopic sinus surgery: a recurrence analysis. An Otol Rhinol Laryngol 120:162-166. View at Publisher |
View at Google Scholar
Smith KA, Orlandi RR, Oakley G, Meeks H, Curtin K, Alt JA. (2019) Long-term revision rates for endoscopic sinus surgery. Int Forum Allergy Rhinol 9:402-408. View at Publisher |
View at Google Scholar
Bachert C, Han JK, Desrosiers M, et al. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomized, double-blind, placebo-controlled, parallel-group phase 3 trials. Lancet 2019; 394:1634-1650. doi: 10.1016/S0140-6736(19)31881-1. View at Publisher |
View at Google Scholar
Gevaert P, Omachi PA, Corren J, Han J, Lee S, Kafman D, Ligueros-Saylan M, Howard M, et al. Efficacy and safety of omalizumab in nasal polyposis: 2 randomized phase 3 trials. J Allergy Clin Immunol 2020; 146(3):595-605. https://doi.org/10.1016/j.jaci.2020.05.032. View at Publisher |
View at Google Scholar
Durán-Lobato M, Niu Z, Alonso MJJAM. Oral delivery of biologics for precision medicine. Adv Mater 2020; 32:1901935. View at Publisher |
View at Google Scholar
Chung SW, Hil-Lal TA, Byun Y. (2012) Strategies for non-invasive delivery of biologics. J Drug Target 20:481-501. View at Publisher |
View at Google Scholar
Osman N, Kaneko K, Carini V, Saleem I. (2018) Carriers for the targeted delivery of aerosolized macromolecules for pulmonary pathologies. Expert Opin Drug Deliv 15(8):821-834. doi: 10.1080/17425247.2018.1502267. View at Publisher |
View at Google Scholar
Sokolowski CJ, Giovannitti JA, Boynes SG. (2010) Needle Phobia: Etiology, Adverse Consequences, and Patient Management. Dent Clin 54:731-744. View at Publisher |
View at Google Scholar
Bodier-Montagutelli E, Mayor A, Vecellio L, Respaud R, Heuzé-Vourc’h N. (2018) Designing inhaled protein therapeutics for topical lung delivery: what are the next steps? Expert Opin Drug Del 15(8):729-736. https://doi.org/10.1080/17425247.2018.1503251. View at Publisher |
View at Google Scholar
Mathews A, Ee PLR, Ge R. (2020) Developing inhaled protein therapeutics for lung diseases. Mol Biomed 1(1):11. doi: 10.1186/s43556-020-00014-z. View at Publisher |
View at Google Scholar
Fröhlich F, Salar-Behzadi S, et al. (2021) Oral inhalation for delivery of proteins and peptides to the lung. Eur J Pharmaceutics Biopharmaceutics 163:198-211. https://doi.org/10.1016/j.ejpb.2021.04.003. View at Publisher |
View at Google Scholar
Liang W, Pan HW, Vllasaliu D, Lam JKW. (2020) Pulmonary delivery of biological drugs: Pharmaceutics 12:1025. doi: 10.3390/pharmaceutics12111025. View at Publisher |
View at Google Scholar
Hacha J, Cataldo DD. (2012) Nebulized anti-IL-13 monoclonal antibody Fab0 fragment reduces allergen-induced asthma. Am J Respir Cell Mol Biol 47:709-717. View at Publisher |
View at Google Scholar
Gozzard N, Lightwood D, Tservistas M, Zehentleitner M, Sarkar K, Turner A, Smith B, Lamour SD, Bourne T, Shaw S, et al. (2017) Novel inhaled delivery of anti-IL-13 MAb (Fab fragment): Preclinical efficacy in allergic asthma. In Proceedings of the European Respiratory Society Annual Congress, Milan, Italy, 9-13 View at Publisher |
View at Google Scholar
Bruns I, Fitzgerald M, Mensing G, Tsung M, Pardali K, Gardiner P, Keeling D, Axelsson L, Olsson M, et al. (2019) Late Breaking Abstract – Multiple ascending dose study of inhaled IL-4Ra antagonist, AZ1402/PRS-060, in mild asthmatics demonstrates robust FeNO reduction and a promising clinical profile for the treatment of asthma. Eur Respir J PA3709. 10.1183/13993003.congress-2019.PA3709. View at Publisher |
View at Google Scholar
Faghihi H, Najafabadi AR, Daman Z, Ghasemian E, Montazeri H, Vatanara A. (2019) Respiratory administration of Infliximab powder for local suppression of inflammation. AAPS PharmSciTech 20:128. 10.1208/s12249-019-1308-0. View at Publisher |
View at Google Scholar
Gauvreau G, Hohlfeld J, Grant S, Jain M, Cabanski M, Pertel P, Boulet L-P, Cockcroft D, Davis B, Fitzgerald J, et al. (2020) Efficacy and safety of an inhaled anti-TSLP antibody fragment in adults with mild atopic asthma. Am J Respir Crit Care Med 201:A4207. doi: 10.11.1164/ajrccm-conference.2020.201.1_MeetingAbstracts.A4207. View at Publisher |
View at Google Scholar
Kerem E, Blau H, Shteinberg M, et al. (2017) WS01.2 phase II clinical trial results of alidornase for the treatment of cystic fibrosis. J Cystic Fibros 16:S1-S16. doi: 10.1016/s1569-1993(17)30157-1. View at Publisher |
View at Google Scholar
Nanus M. (2017) Protalix BioTherapeutics announces phase II clinical trial results for alidornase alfa in cystic fibrosis presented at the 40th European Cystic Fibrosis Society Conference. Protalix BioTherapeutics. https://protalixbiotherapeutics.gcs-web.com/news-releases/news-release-details/protalix-biotherapeutics-announces-phase-ii-clinical-trial. Published. View at Publisher |
View at Google Scholar
Sorrells S, Camprubi S, Griffin R, Chen J, Ayguasanova J. (2015) SPARTA clinical trial design: Exploring the efficacy and safety of two dose regimens of alpha 1-proteinase inhibitor augmentation therapy in alpha 1-antitrypsin deficiency. Respir Med 109:490-499. View at Publisher |
View at Google Scholar
Campo I, Mariani Fet al. (2016) Inhaled sargramostim and whole lung lavage (WLL) as therapy of autoimmune pulmonary alveolar proteinosis (aPAP). Eur Respir J 48:PA3870. 10.1183/13993003.congress-2016.PA3870. View at Publisher |
View at Google Scholar
Tazawa R, Ueda M, Abe M, Tatsumi K, Eda R, Kondoh S, Morimoto K, Tanaka E, Yamaguchi E, Takahashi A, et al. (2019) Inhaled GM-CSF for pulmonary alveolar proteinosis. N Engl J Med 381:923-932. 10.1056/NEJMoa1816216. View at Publisher |
View at Google Scholar
Maillet A, Guilleminault L, Legrain B, et al. (2011) The airways: a novel route for delivering monoclonal antibodies to treat lung tumors. Pharm Res 28:2147-2156. View at Publisher |
View at Google Scholar
Guilleminault L, Azzopradi N, et al. (2014) Fate of inhaled monoclonal antibodies after deposition of aerosolized particles in the respiratory system. J Control Release 196:344-354. View at Publisher |
View at Google Scholar
Hanke L, Perez LV, Sheward DJ, Das H, Schulte T, Moliner-Morro A, Corcoran M, Achour A, Hedestam GBK, Hallberg BM, et al. An alpaca nanobody neutralizes SARS-CoV-2 by blocking receptor interaction. Nat Commun. View at Publisher |
View at Google Scholar
Konwarh R. Nanobodies: Prospects of Expanding Gamut of Neutralizing Antibodies Against the Novel Coronavirus, SARS-CoV-2. Front Immunol 2020; 11:1531. View at Publisher |
View at Google Scholar
BioSpace. (2020) Ansun Biopharma enrols first patient in proof of concept trial of DAS181 for the treatment of COVID-19. https://www.biospace.com/article/releases/ansun-biopharma-enrolls-first-patient-in-proof-of-concept-trial-of-das181-for-the-treatment-of-covid-19/. Published. View at Publisher |
View at Google Scholar
White S, Bennett DB, Cheu S. (2005) Exuberafi: Pharmaceutical Developmant of a Novel Product for Pulmonary Delivery of Insulin. Diabetes Technol Ther 7:896-906. View at Publisher |
View at Google Scholar
Cassidy JP, Amin N, Marino M, Gotfried M, Meyer T, Sommerer K, Baughman RA. (2011) Insulin Lung Deposition and Clearance Following TechnospherefiInsulin Inhalataion powder Administration. Pharm Res 28:2157-2164. View at Publisher |
View at Google Scholar
Klonoff DC. Afrezza inhaled insulin: The fastest-acting FDA-approved insulin on the market has favourable properties. J Diabetes Sci Technol 2014; 8:1071-1073. View at Publisher |
View at Google Scholar
Dumont JA, Bitonti AJ, Clark D, Evans S, Pickford M, Newman SP. Delivery of an Erythropoietin-Fc Fusion Protein by Inhalation in Humans through an Immunoglobulin Transport Pathway. J Aerosol Med 2005; 18:294-3003. View at Publisher |
View at Google Scholar
Vallee S, Rakhe S, Reidy T, Walker S, Lu Q, Sakorafas P, Low S, Bitonti A. (2012) Pulmonary Administration of Interferon Beta-1a-Fc Fusion Protein in Non-Human Primates Using an Immunoglobulin Transport pathway. J Interf Cytokine Res 32:178-184. View at Publisher |
View at Google Scholar
Agu R, Ugwoke MI; Armand M, Kinget R, Verbeke N. (2001) The lung as a route for systemic delivery of therapeutic proteins and peptides. Respir Res 2:198-209. View at Publisher |
View at Google Scholar
Burgess G, Boyce M, Jones M, Larsson L, Main MJ, Morgan F, Phillips P, Scrimgeour A, Strimenopoulou F, Vajjah P, et al. (2018) Randomized study of the safety and pharmacodynamics of inhaled interleukin-13 monoclonal antibody fragment VR942. EBioMedicine 35:67-75. View at Publisher |
View at Google Scholar
Pilcer G, Amighi K. (2010) Formulation strategy and use of excipients in pulmonary drug delivery. Int J Pharm 392:1-19. View at Publisher |
View at Google Scholar
Carvalho TC, Peters JI, Williams RO, III. Influence of particle size on regional lung deposition – What evidence is there. Int J Pharm 2011; 406:1-10. View at Publisher |
View at Google Scholar
Ibrahim M, Verma R, Garcia-Contreras L. (2015) Inhalation drug delivery devices: technology update. Med Devices 8:131-139. View at Publisher |
View at Google Scholar
Jones RGA, Landon J. (2003) A protocol for ‘enhanced pepsin digestion’: A step by step method for obtaining pure antibody fragments in high yield from serum. J Immunol Methods 275:230-250. View at Publisher |
View at Google Scholar
Guichard M-J, Leal T, Vanbever R. PEGylation an approach for improving the pulmonary delivery of biopharmaceuticals. Curr Opin Colloid Interface Sci 2017; 31:43-50. View at Publisher |
View at Google Scholar
Cantin AM, Woods DE, Cloutier D, Dufour EK, Leduc R. Polyethylene glycol conjugation at Cys 232 prolongs half-life of α 1 proteinase inhibitor. Am J Respir Cell Mol Biol 2002; 27:659-665. View at Publisher |
View at Google Scholar
McLeod VM, Chan LJ, Ryan GM, Porter CJ, Kaminskas LM, et al. Optimal PEGylation can improve the exposure of interferon in the lungs following pulmonary administration. J Pharm Sci 2015; 104:1421-1430. View at Publisher |
View at Google Scholar
Koussoroplis SJ, Paulissen G, Tyteca D, Goldansaz H, Todoroff J, Barilly C, Uyttenhove C, Van Snick J, Cataldo DD, Vanbever R. PEGylation of antibody fragments greatly increases their local residence time following delivery to the respiratory tract. J Control Release 2014; 187:91-100. View at Publisher |
View at Google Scholar
Patil HP, Freches D, Karmani L, Duncan GA, Ucakar B, Suk JS, Hanes J, Gallez B, Vanbever R. Fate of PEGylated antibody fragments following delivery to the lungs: influence of delivery site, PEG size and lung inflammation. J Control Release 2018; 272:62-71. View at Publisher |
View at Google Scholar
Lamche H, Meade C, Zierenberg B, Reimholz R. Process for nebulizing aqueous compositions containing highly concentrated insulin. U.S. Patent US20030064032A1. Issued 6. Nov. 2002. View at Publisher |
View at Google Scholar
Morales JO, Fathe KR, Brunaugh A, Ferrati S, Li S, Montenegro-Nicolini M, et al. Challenges and future prospects for the delivery of biologics: oral mucosal, pulmonary, and transdermal routes. AAPS J 2017; 19(3):652-668. doi: 10.1208/s12248-017-0054-z. View at Publisher |
View at Google Scholar
Deller D, Thipphawong B, Otulana B, Caplan D, Ericson L, Milgram J, Okikawa J, Bowman QCM. Bolus inhalation of rhDNase with the AERx system in subjects with cystic fibrosis. J Aerosol Med 2003; 16:175-182. View at Publisher |
View at Google Scholar
Sangwan S, Agosti JM, Bauer LA, Otulana BA, Morishige RJ, Cipolla DC, Blanchard JD, Smaldone GC. Aerosolized protein delivery in asthma: gamma camera analysis of regional deposition and perfusion. J Aerosol Med 2001; 14:185-195. View at Publisher |
View at Google Scholar
Hollander PA, Blonde L, Rowe R, Mehta AE, Milburn JL, Hershon KS, Chiasson J-L, Levin SR. Efficacy and safety of inhaled insulin (exubera) compared with subcutaneous insulin therapy in patients with type 2 diabetes: Results of a 6-month, randomized, comparative trial. Diabetes Care 2004; 27:2356-2362. View at Publisher |
View at Google Scholar
Colombo RE, Fiorentino C, Dodd LE, Hunsberger S, Haney C, Barrett K, Nabha L, Davey RT, Jr. Olivier KN. A phase 1 randomized, double-blind, placebo-controlled, crossover trial of DAS181 (Fludasefi) in adult subjects with well-controlled asthma. BMC Infect Dis 2015; 16:1-10. View at Publisher |
View at Google Scholar
Syabbalo N. The role of thymic stromal lymphopoietin in the pathogenesis and treatment of severe uncontrolled asthma. J Lung 2021; 2(3):6931. View at Publisher |
View at Google Scholar
Fahy JV, Cockroft DW, Boulet L-P, Wong HH, Deschesnes F, Davis EE, Ruppel J, Su JQ, Adelman DC. Effects of aerosolized anti-IgE (E25) on airway responses to inhaled allergen in asthmatic subjects. J Respir Crit Care Med 1999; 160:1023-1027. View at Publisher |
View at Google Scholar
Matschiner G, Huang S, Constant S, Rattenstetter B, Gille H, Hohlbaun AM, Koller B, Keeling D. Fitzgerald M. The discovery and development of AZD1402/PRS-060, an inhaled, potent and selective antagonist of IL-4 receptor alpha. Airway Pharmacol Treat 2018; 52:PA1047. View at Publisher |
View at Google Scholar
Burns I, Fitzgerald MF, Pardali K, Gardiner P, Keeling D, Axelsson L. Jiamg F, Lickliter J, Close D. First-in-human data for the inhaled IL-4R antagonist AZD1402/PRS-060 reveals a promising clinical profile for the treatment of asthma. Am J Respir Crit Care Med 2019; 199:A7476. View at Publisher |
View at Google Scholar
Freches D, Patil HP, Franco MM, Uyttenhove C, Heywood S, Vanbever R. PEGylation prolongs the pulmonary retention of an anti-IL-17A Fab’ antibody fragment after delivery in three different species. Int J Pharm 2017; 521:120-129. View at Publisher |
View at Google Scholar
Gauvreau G, Hohfeld J, Boulet L-P, Cockcroft D, Davis B, Fitzgerald JM, Korn S, Kornmann O, Leigh R, et al. Late Breaking Abstract – Efficacy of CSJ117 on allergen-induced asthmatic responses in mild atopic asthma patients. Eur Respir J 2020; 56:3690. DOI: 10.1183/13993003.congress-2022.3690. View at Publisher |
View at Google Scholar
Dear Jessica, and the super professional team of the ‘Clinical Cardiology and Cardiovascular Interventions’
I am sincerely grateful to the coordinated work of the journal team for the no problem with the submission of my manuscript: “Cardiometabolic Disorders in A Pregnant Woman with Severe Preeclampsia on the Background of Morbid Obesity (Case Report).”
The review process by 5 experts was fast, and the comments were professional, which made it more specific and academic, and the process of publication and presentation of the article was excellent.
I recommend that my colleagues publish articles in this journal, and I am interested in further scientific cooperation.
Sincerely and best wishes,
Dr. Oleg Golyanovskiy.
Dr Oleg Golyanovski
Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.
Virginia E. Koenig
Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases.
Thank you for all.
Delcio G Silva Junior
Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article.
Specially thank you for the peer review process, support from the editorial office.
I appreciate positively the quality of your journal.
Ziemlé Clément Méda
Journal of Clinical Research and Reports
I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office.
The reviewer board were accurate and helpful regarding any modifications for my manuscript.
And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help.
It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.
Mina Sherif Soliman Georgy
We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work.
Hope for a more scientific relationship with your Journal.
Layla Shojaie
The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.
Sing-yung Wu
Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.
Orlando Villarreal
Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.
Katarzyna Byczkowska
Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.
Anthony Kodzo-Grey Venyo
Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.
Pedro Marques Gomes
Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.
Bernard Terkimbi Utoo
This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.
Prof Sherif W Mansour
Dear Hao Jiang, to Journal of Nutrition and Food Processing
We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.
Hao Jiang
As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal.
The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage.
The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful.
The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders.
In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dr Shiming Tang
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery,
Editorial Coordinator,
I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office.
The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
Raed Mualem
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Andreas Filippaios
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity.
The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
Dr Suramya Dhamija
Dear Erica Kelsey,
Editorial Coordinator of Cancer Research and Cellular Therapeutics
Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications.
We appreciated the very short time between the submission of the paper and its publication on line on your site.
Bruno Chauffert
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article.
Have a good day!
Baheci Selen
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
Jesus Simal-Gandara
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far.
Keep up the great work.
Douglas Miyazaki
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
Dr Griffith
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
Dr Tong Ming Liu
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
Husain Taha Radhi
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery.
The peer review process, support from the editorial office, and quality of the journal are excellent.
The manuscripts published are of high quality and of excellent scientific value.
I recommend this journal very much to colleagues.
S Munshi
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
Tania Munoz
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
George Varvatsoulias
Dear editorial department:
On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal.
Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner.
I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality.
Sincerely,
Rui Tao.
Rui Tao
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
Khurram Arshad
Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.
Gomez Barriga Maria Dolores
The peer reviewers process is quick and effective, the supports from editorial office is excellent,
the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.
Lin Shaw Chin
Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project.
I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality.
We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.
Maria Dolores Gomez Barriga
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions,
I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients."
I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.
Dr Maria Dolores Gomez Barriga
Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing.
¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.
Dr Maria Regina Penchyna Nieto
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions,
The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed.
The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.
Dr Marcelo Flavio Gomes Jardim Filho
Dear Editorial Coordinator of the Journal of Nutrition and Food Processing!
"I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”
Zsuzsanna Bene
Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner
Dr Susan Weiner
My Testimonial Covering as fellowing: Lin-Show Chin.
The peer reviewers process is quick and effective, the supports from editorial office is excellent,
the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews.
Lin-Show Chin
My experience publishing in Psychology and Mental Health Care was exceptional.
The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work.
The editorial team was highly supportive and responsive, making the submission process smooth and efficient.
The journal's commitment to high standards and academic rigor makes it a respected platform for quality research.
I am grateful for the opportunity to publish in such a reputable journal.
Sonila Qirko
My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional.
I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.
Luiz Sellmann
I would like to offer my testimony in the support. I have received through the peer review process and support the editorial office where they are to support young authors like me, encourage them to publish their work in your esteemed journals, and globalize and share knowledge globally. I really appreciate your journal, peer review, and editorial office.
Zhao Jia
Dear Agrippa Hilda- Editorial Coordinator of Journal of Neuroscience and Neurological Surgery,
"The peer review process was very quick and of high quality, which can also be seen in the articles in the journal. The collaboration with the editorial office was very good."
Thomas Urban
I would like to express my sincere gratitude for the support and efficiency provided by the editorial office throughout the publication process of my article, “Delayed Vulvar Metastases from Rectal Carcinoma: A Case Report.” I greatly appreciate the assistance and guidance I received from your team, which made the entire process smooth and efficient.
The peer review process was thorough and constructive, contributing to the overall quality of the final article. I am very grateful for the high level of professionalism and commitment shown by the editorial staff, and I look forward to maintaining a long-term collaboration with the International Journal of Clinical Case Reports and Reviews.
Cristina Berriozabal
To Dear Erin Aust,
I would like to express my heartfelt appreciation for the opportunity to have my work published in this esteemed journal. The entire publication process was smooth and well-organized, and I am extremely satisfied with the final result. The Editorial Team demonstrated the utmost professionalism, providing prompt and insightful feedback throughout the review process. Their clear communication and constructive suggestions were invaluable in enhancing my manuscript, and their meticulous attention to detail and dedication to quality are truly commendable.
Additionally, the support from the Editorial Office was exceptional. From the initial submission to the final publication, I was guided through every step of the process with great care and professionalism. The team's responsiveness and assistance made the entire experience both easy and stress-free.
I am also deeply impressed by the quality and reputation of the journal. It is an honor to have my research featured in such a respected publication, and I am confident that it will make a meaningful contribution to the field.
Dr Tewodros Kassahun Tarekegn
"I am grateful for the opportunity of contributing to [International Journal of Clinical Case Reports and Reviews] and for the rigorous review process that enhances the quality of research published in your esteemed journal. I sincerely appreciate the time and effort of your team who have dedicatedly helped me in improvising changes and modifying my manuscript. The insightful comments and constructive feedback provided have been invaluable in refining and strengthening my work".
Dr Shweta Tiwari
I thank the ‘Journal of Clinical Research and Reports’ for accepting this article for publication. This is a rigorously peer reviewed journal which is on all major global scientific data bases. I note the review process was prompt, thorough and professionally critical. It gave us an insight into a number of important scientific/statistical issues. The review prompted us to review the relevant literature again and look at the limitations of the study. The peer reviewers were open, clear in the instructions and the editorial team was very prompt in their communication.
This journal certainly publishes quality research articles.
I would recommend the journal for any future publications.
Dr Farooq Wandroo
Dear Jessica Magne, with gratitude for the joint work. Fast process of receiving and processing the submitted scientific materials in “Clinical Cardiology and Cardiovascular Interventions”. High level of competence of the editors with clear and correct recommendations and ideas for enriching the article.
Dr Anyuta Ivanova
We found the peer review process quick and positive in its input. The support from the editorial officer has been very agile, always with the intention of improving the article and taking into account our subsequent corrections.
Dr David Vinyes
My article, titled 'No Way Out of the Smartphone Epidemic Without Considering the Insights of Brain Research,' has been republished in the International Journal of Clinical Case Reports and Reviews. The review process was seamless and professional, with the editors being both friendly and supportive. I am deeply grateful for their efforts.
Gertraud Teuchert-Noodt
To Dear Erin Aust – Editorial Coordinator of Journal of General Medicine and Clinical Practice!
I declare that I am absolutely satisfied with your work carried out with great competence
in following the manuscript during the various stages from its receipt,
during the revision process to the final acceptance for publication.
Thank
Prof. Elvira Farina
Dr Elvira Farina
Dear Jessica, and the super professional team of the ‘Clinical Cardiology and Cardiovascular Interventions’
I am sincerely grateful to the coordinated work of the journal team for the no problem with the submission of my manuscript: “Cardiometabolic Disorders in A Pregnant Woman with Severe Preeclampsia on the Background of Morbid Obesity (Case Report).”
The review process by 5 experts was fast, and the comments were professional, which made it more specific and academic, and the process of publication and presentation of the article was excellent.
I recommend that my colleagues publish articles in this journal, and I am interested in further scientific cooperation.
Sincerely and best wishes,
Dr. Oleg Golyanovskiy.
Dr Oleg Golyanovski
Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.
